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- Title
Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice.
- Authors
Chung, Chi-Li; Chen, Jui-Hsuan; Huang, Wei-Chieh; Sheu, Joen-Rong; Hsia, Chih-Wei; Jayakumar, Thanasekaran; Hsia, Chih-Hsuan; Chiou, Kuan-Rau; Hou, Shaw-Min
- Abstract
Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin's effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca2+ ([Ca2+]i) mobilization and thromboxane A2 formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3β and MAPK pathways; this leads to a reduction in [Ca2+]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.
- Subjects
BLOOD platelet activation; BLOOD platelets; PHOSPHATIDYLINOSITOL 3-kinases; BLOOD platelet aggregation; MITOGEN-activated protein kinases; PULMONARY embolism; FLAVONOIDS; ADENOSINE triphosphate
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 19, p11372
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms231911372